Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate

摘要

Neurogenin3isessentialforenteroendocrinecelldevelopment;however,itisunknownwhetherthistranscriptionfactorissufficienttoinduceanendocrineprogramintheintestineorhowitaffectsthedevelopmentofotherepithelialcellsoriginatingfromcommonprogenitors.Inthisstudy,themousevillinpromoterwasusedtodriveNeurogenin3expressionthroughoutthedevelopingepitheliumtomeasuretheaffectoncellfate.Althoughthegeneralmorphologyoftheintestinewasunchanged,transgenicfounderembryosdisplayedincreasednumbersofcellsexpressingthepan-endocrinemarkerchromograninA.Accordingly,expressionofseveralhormonesandpro-endocrinetranscriptionfactorswasincreasedinthetransgenicssuggestingthatNeurogenin3stimulatedaprogramofterminalenteroendocrinecelldevelopment.Totestwhetherincreasedendocrinecelldifferentiationaffectedthedevelopmentofothersecretorycelllineages,wequantifiedgobletcells,theonlyothersecretorycellformedinembryonicintestine.TheNeurogenin3-expressingtransgenicshaddecreasednumbersofgobletcellsincorrespondencetotheincreaseinendocrinecells,withnochangeinthetotalsecretorycellnumbers.Thus,ourdatasuggestthatNeurogenin3canredirectthedifferentiationofbipotentialsecretoryprogenitorstoendocrineratherthangobletcellfate./p/div